1-16148628-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004431.5(EPHA2):c.573G>A(p.Leu191Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,607,608 control chromosomes in the GnomAD database, including 86,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6602 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80154 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.414

Publications

24 publications found

Variant links:

Genes affected

EPHA2 (HGNC:3386): (EPH receptor A2) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]

EPHA2 Gene-Disease associations (from GenCC):

cataract 6 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
early-onset non-syndromic cataract
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior polar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior subcapsular cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EPHA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-16148628-C-T is Benign according to our data. Variant chr1-16148628-C-T is described in ClinVar as Benign. ClinVar VariationId is 259394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.414 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004431.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA2	NM_004431.5	MANE Select	c.573G>A	p.Leu191Leu	synonymous	Exon 3 of 17	NP_004422.2
	EPHA2	NM_001329090.2		c.411G>A	p.Leu137Leu	synonymous	Exon 2 of 16	NP_001316019.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPHA2	ENST00000358432.8	TSL:1 MANE Select	c.573G>A	p.Leu191Leu	synonymous	Exon 3 of 17	ENSP00000351209.5
EPHA2	ENST00000917106.1		c.573G>A	p.Leu191Leu	synonymous	Exon 3 of 17	ENSP00000587165.1
EPHA2	ENST00000863593.1		c.573G>A	p.Leu191Leu	synonymous	Exon 3 of 17	ENSP00000533652.1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42280

AN:

151972

Hom.:

6594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.320

GnomAD2 exomes

AF:

0.298

AC:

73530

AN:

246468

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0176

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.324

AC:

472241

AN:

1455518

Hom.:

80154

Cov.:

AF XY:

0.326

AC XY:

236464

AN XY:

724360

show subpopulations

African (AFR)

AF:

0.166

AC:

5571

AN:

33478

American (AMR)

AF:

0.331

AC:

14783

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10512

AN:

26134

East Asian (EAS)

AF:

0.0238

AC:

945

AN:

39700

South Asian (SAS)

AF:

0.338

AC:

29155

AN:

86244

European-Finnish (FIN)

AF:

0.278

AC:

13161

AN:

47324

Middle Eastern (MID)

AF:

0.450

AC:

2595

AN:

5768

European-Non Finnish (NFE)

AF:

0.339

AC:

376377

AN:

1111844

Other (OTH)

AF:

0.317

AC:

19142

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

23057

46114

69171

92228

115285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11954

23908

35862

47816

59770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.278

AC:

42299

AN:

152090

Hom.:

6602

Cov.:

AF XY:

0.277

AC XY:

20598

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.165

AC:

6855

AN:

41524

American (AMR)

AF:

0.345

AC:

5273

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1394

AN:

3464

East Asian (EAS)

AF:

0.0239

AC:

124

AN:

5186

South Asian (SAS)

AF:

0.327

AC:

1581

AN:

4832

European-Finnish (FIN)

AF:

0.273

AC:

2889

AN:

10580

Middle Eastern (MID)

AF:

0.462

AC:

135

AN:

292

European-Non Finnish (NFE)

AF:

0.340

AC:

23069

AN:

67932

Other (OTH)

AF:

0.322

AC:

680

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1550

3099

4649

6198

7748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.312

Hom.:

6957

Bravo

AF:

0.274

Asia WGS

AF:

0.192

AC:

668

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 6 multiple types (3)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.3

(source)

DANN

Benign

0.92

PhyloP100

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over